外周血相关指标对晚期尿路上皮癌患者一线PD-1单抗治疗疗效的预测价值

Value of peripheral blood indicators for predicting efficacy of first-line anti-PD-1 therapy to patients with advanced urothelial carcinoma

背景免疫治疗给尿路上皮癌(urothelial carcinoma,UC)患者带来的生存获益令人鼓舞,但目前尚缺乏成熟的筛选免疫治疗获益人群的预测指标。目的 探索外周血相关指标预测PD-1单抗治疗晚期UC患者的疗效及生存预后的价值,为临床应用提供一定的实践经验。方法 收集解放军总医院第一医学中心肿瘤内科2017年3月-2020年4月接受一线PD-1单抗治疗的晚期UC患者。分析治疗前后外周血各项指标(以中位数为切点转化为二分类指标)与免疫治疗疗效之间的相关性,并评估相关指标对中位无进展生存期(progression-free survival,PFS)的预测价值。结果 共纳入患者46例,男性32例,女性14例,中位年龄64岁。一线接受PD-1单抗治疗的46例患者中位PFS为10.5(3~22)个月。治疗6周后的外周血高血红蛋白(hemoglobin,Hb)组(15.0个月vs 6.6个月)、低中性粒细胞-淋巴细胞比值(neutrophil-to-lymphocyte ratio,NLR)组(未达到vs 6.6个月)、低系统免疫炎症指数(systemic immune-inflammation index,SII)组(15.0个月vs 6.6个月)患者的PFS显著延长(P<0.05)。Cox分析结果显示,治疗6周后的Hb、NLR和SII是患者预后的显著影响因素(P均<0.05)。ROC分析显示:治疗后6周的Hb、NLR、SII预测预后的AUC(95%CI)分别为0.760(0.570~0.943)、0.698(0.435~0.958)、0.666(0.391~0.944),均对接受免疫治疗患者的预后具有一定预测效能。结论 开始接受免疫治疗6周后的Hb、NLR和SII对晚期UC患者免疫治疗的疗效及预后具有预测价值,可能是晚期UC患者对一线PD-1单抗治疗产生应答的生物标志物。

Background The survival benefit of immunotherapy in the treatment of urothelial carcinoma is inspiring, but there is still a lack of effective predictors for screening patients benefiting from immunotherapy. Objective To explore the value of peripheral blood related indicators in predicting the efficacy and survival prognosis of anti-PD-1 therapy for patients with advanced UC, and provide practical experience for clinical application. Methods Totally 46 patients with advanced UC who received first-line anti-PD-1 therapy from March 2017 to April 2020 in the Department of Oncology, the First Medical Center of Chinese PLA General Hospital were collected. The correlation between the peripheral blood related indicators at baseline and at 6 weeks after treatment and the efficacy of anti-PD-1 was statistically analyzed. The value of related indicators in predicting efficacy and prognosis was evaluated. Results There were 32 males and 14 females, with a median age of 64 years. Of the 46 patients who received first-line anti-PD-1 therapy, the median PFS was 10.5 months(3 to 22 months). At 6 weeks after treatment, PFS of the high Hb group(15.0 months vs 6.6 months), the low neutrophil-to-lymphocyte ratio(NLR) group(not reach vs 6.6 months) and the low systemic immune-inflammation index(SII) group(15.0 mongths vs 6.6 months) were significantly prolonged(P<0.05). Cox analysis showed that Hb, NLR and SII after 6 weeks of treatment were associated with the prognosis of patients(all P<0.05). ROC analysis showed that the ROC-AUC(95% CI) of Hb, NLR and SII was 0.760(0.570-0.943), 0.698(0.435-0.958) and 0.666(0.391-0.944),respectively, all of which had certain predictive value for patients receiving immunotherapy. Conclusion Hb, NLR and SII at 6 weeks after treatment have predictive value for the efficacy and prognosis of immunotherapy in patients with advanced UC and may be biomarkers for the response of patients to first-line anti-PD-1 therapy.